Influenza B virus neuraminidase: a potential target for next-generation vaccines?

ABSTRACT

Introduction

Influenza B viruses (IBV) cause a significant health and economic burden annually. Due to lower antigenic drift rate, less extensive antigenic diversity, and lack of animal reservoirs, the development of highly effective universal vaccines against IBV might be in reach. Current seasonal influenza vaccines are formulated to induce antibodies against the Hemagglutinin (HA) protein, but their effectiveness is reduced by mismatch between vaccine and circulating strains.

Areas covered

Given antibodies against the Neuraminidase (NA) have been associated with protection during influenza infection, there is considerable interest in the development of NA-based influenza vaccines. This review summarizes insights into the role of NA-based immunity against IBV and highlights knowledge gaps that should be addressed to inform the design of next-generation influenza B vaccines. We discuss how antibodies recognize broadly cross-reactive epitopes on the NA and the lack of understanding of IBV NA antigenic evolution which would benefit vaccine development in the future.

Expert opinion

Demonstrating NA antibodies as correlates of protection for IBV in humans would be paramount. Determining the extent of IBV NA antigenic evolution will be informative. Finally, it will be critical to determine optimal strategies for incorporating the appropriate NA antigens in existing clinically approved vaccine formulations.

KEYWORDS:

• Antibodies
• influenza B virus
• neuraminidase
• universal vaccines
• antigenic evolution

Article highlights

• NA-specific antibodies are a correlate of protection from influenza disease.

• NA-based vaccines are broadly protective against IBV in animal models.

• Broadly cross-reactive monoclonal antibodies against the NA define universal epitopes at the enzymatic active site of NA.

• Antigenic evolution of IBV NA is poorly characterized.

• Various strategies exist to induce NA-specific antibodies by vaccination.

Declaration of interests

M. Koutsakos has acted as a consultant for Sanofi group of companies. The other authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants, or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

THTD and MK drafted the manuscript. AKW and SK revised the manuscript.

Additional information

Funding

This manuscript was funded by the Morningside Foundation and by Australian National Health and Medical Research Council Investigator grants.